Wnt Signaling Regulates Hepatic Metabolism

• DOI: 10.1126/scisignal.2001249
• Publication Date: 2011-02-01T21:23:37Z
• Authors: Hongjun Liu; Maria M. Fergusson; J. Julie Wu; Ilsa I. Rovira; Jie Liu; Oksana Gavrilova; Teng Lu; Jianjun Bao; Donghe Han; Michael N. Sack; Toren Finkel
• Keywords: Cell Signaling

The contribution of the Wnt pathway has been extensively characterized in embryogenesis, differentiation, and stem cell biology but not mammalian metabolism. Here, using vivo gain- loss-of-function models, we demonstrate an important role for signaling hepatic In particular, β-catenin, downstream mediator canonical signaling, altered serum glucose concentrations regulated production. β-Catenin also modulated insulin signaling. Furthermore, β-catenin interacted with transcription factor FoxO1 livers from mice under starved conditions. interaction transcriptional activation genes encoding glucose-6-phosphatase (G6Pase) phosphoenolpyruvate carboxykinase (PEPCK), two rate-limiting enzymes gluconeogenesis. Moreover, starvation induced expression mRNAs different isoforms. addition, nutrient deprivation appeared to favor association FoxO family members, rather than members T activators. Notably, a model diet-induced obesity, deletion improved overall metabolic homeostasis. These observations implicate modulation metabolism raise possibility that may play similar regulation other tissues.